Inhalation of silica results in chronic inflammation and fibrosis with a decrease in lung function and an increase in susceptibility to autoimmune diseases. The disease process involved in silicosis has been linked with mediators from both the Th1 and Th2 arms of immunity, and evidence suggests each plays a distinct role. Specifically, Th1 inflammation is upregulated in the acute phase, while Th2 cytokines have been associated with fibrosis in the later stages. A major component of lung immunology is the pulmonary macrophage. Macrophages have the ability to regulate immune responses by playing the role of intermediary between the innate and adaptive immune systems. Alveolar macrophages (AM) have been implicated as a vital role in silicosis, including reportedly phagocytic uptake of silica. Recently, a subset of macrophages, alternatively activated (aaMac), has been associated with Th2-dominated immunity. This proposal will determine the role of aaMac following silica exposure, and the mechanism involved in the switch from Th1 inflammation to Th2-directed fibrosis in the later stages of silicosis. [unreadable] [unreadable] [unreadable]